Phosphoinositide 3-kinase γ mediates microglial phagocytosis via lipid kinase-independent control of cAMP.
Neuroscience
; 233: 44-53, 2013 Mar 13.
Article
en En
| MEDLINE
| ID: mdl-23276671
ABSTRACT
Microglial phagocytosis plays a key role in neuroprotective and neurodegenerative responses of the innate immune system in the brain. Here we investigated the regulatory function of phosphoinositide 3-kinase γ (PI3Kγ) in phagocytosis of bacteria and Zymosan particles by mouse brain microglia in vitro and in vivo. Using genetic and pharmacological approaches our data revealed PI3Kγ as an essential mediator of microglial phagocytosis. Unexpectedly, microglia expressing lipid kinase deficient mutant PI3Kγ exhibited similar phagocytosis as wild-type cells. These data suggest kinase-independent stimulation of cAMP phosphodiesterase activity by PI3Kγ as a crucial mediator of phagocytosis. In sum our findings indicate PI3Kγ-dependent suppression of cAMP signaling as a critical regulatory element of microglial phagocytosis.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fagocitosis
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Encéfalo
/
Microglía
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Fosfodiesterasas de Nucleótidos Cíclicos Tipo 3
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Fosfatidilinositol 3-Quinasa Clase Ib
Límite:
Animals
Idioma:
En
Revista:
Neuroscience
Año:
2013
Tipo del documento:
Article
País de afiliación:
Alemania